A study on the surface properties of human peripheral blood lymphocytes is in progress. The nature of the linkage of the membrane- bound sialic acid is being explored by treatment with a variety of neuraminidases. Surface carboxyl group analysis after aldehyde fixation is being carried out by methylation with either methanolic HCl, carbodiimides, ethylene imine or diazomethane. Surface amino group analysis is being performed on the native lymphocyte using 2- methylmaleic anhydride and 2,3-dimethylmaleic anhydride. Sulfhydryl groups are being replaced on the native lymphocyte by means of 6-6' dithiodinicotinic acid which replaces the SH groups with the appropriate number of carboxyl groups. The distribution of erythrocyte membrane associated glycoproteins is being investigated by treatment of intact human red blood cells, ghosts and ghosts solubilized with either SDS or guanidine HCL with alpha-chymotrypsin, trypsin and neuraminidase. The resulting enzyme digests are being analyzed for peptide content, carbohydrate, hexosamine and sialic acid in order to determine the enzymic accessibility of some of the membrane gycoproteins.